Disease relevance of Pank1

• Patients with Hallervorden-Spatz syndrome, an autosomal recessive, progressive neurodegenerative disorder, have mutations in a novel pantothenate kinase gene (PANK2) [1].

High impact information on Pank1

• Pantothenate kinase catalyzes a key regulatory step in coenzyme A biosynthesis, and there are four mammalian genes that encode isoforms of this enzyme [2].
• To date, molecular cloning of enzymes involved in the CoA biosynthetic pathway in mammals has been only reported for pantothenate kinase [3].
• Chemical knockout of pantothenate kinase reveals the metabolic and genetic program responsible for hepatic coenzyme a homeostasis [4].
• Instead, pantothenol inhibited the in vitro growth of P. falciparum via a mechanism that involves competition with pantothenate and which can be attributed to inhibition of the parasite's pantothenate kinase [5].
• fumble encodes a pantothenate kinase homolog required for proper mitosis and meiosis in Drosophila melanogaster [6].

Biological context of Pank1

• The PanK1 beta transcript begins with exon 1 beta and translates into a ten-residue amino terminus plus the catalytic domain [7].
• The mouse murine pantothenate kinase (Pank1) gene consists of seven introns and eight exons and is located on chromosome 19 (19C2-3) [7].

Anatomical context of Pank1

• Pantothenate kinase activity in livers of genetically diabetic mice (db/db) and hormonally treated cultured rat hepatocytes [8].

Associations of Pank1 with chemical compounds

• Pantothenate kinase (PanK) is the key regulatory enzyme in the CoA biosynthetic pathway in bacteria and is thought to play a similar role in mammalian cells [9].
• Liver PAK from genetically diabetic mice was inhibited by acetyl-CoA to the same extent as enzyme from nondiabetic mice and by CoASH to nearly the same extent [8].
• These changes were accompanied by significant decreases in pantothenate and increases in 4-phosphopantothenate suggesting an increase in pantothenate kinase activity due to reduction of CoA inhibition of the enzyme [10].
• Findings support the CoA depletion mechanism of valproate inhibition of beta-oxidation and other CoA- and acetyl CoA-requiring enzymic reactions and stress the role of carnitine in the regulation of CoA synthesis at the site of action of pantothenate kinase [11].

References